ANTAGONISM OF CISPLATIN INDUCED EMESIS IN THE DOG

Abstract

Cisplatin (cis-diammine-dichloro-platinum) [an antineoplastic drug] administered at a dose of 3 mg/kg i.v. induced a reproducible and characteristic emetic response in the dog. It was characterized by a latency period (90-120 min) and multiple emetic episodes occurring within 5 h following drug administration with sporadic delayed emesis later within the first 24 h. There was a qualitative similarity between the emetic response of cisplatin seen in dogs and cancer patients. Metoclopramide (1 and 3 mg/kg s.c.) was the most effective antagonist of cisplatin emesis in the dog while haloperidol (1 mg/kg s.c.) and chlorpromazine (0.3, 1 and 3 mg/kg s.c.) offered a less complete protection. Nabilone (0.1 mg/kg i.v.) and AL-1612 [3-ethyl-5(4,4-ethylene dioxypiperidine-1-methyl)-6,7-dihydro-2-methylindol-4(5H)-one sulfate] (1 mg/kg s.c.) failed to demonstrate any significant activity. A relationship between antagonism patterns of emetic responses induced by cisplatin and apomorphine was discussed.